Cilostazol and isosorbide mononitrate for the prevention of progression of cerebral small vessel disease: baseline data and statistical analysis plan for the Lacunar Intervention Trial-2 (LACI-2) (ISRCTN14911850)

Bath, Philip M.; Mhlanga, Iris; Woodhouse, Lisa J.; Doubal, Fergus; Oatey, Katherine; Montgomery, Alan A.; Wardlaw, Joanna M.; LACI-2 Trial Investigators

Abstract

Background: Cerebral small vessel disease (SVD) causes lacunar strokes (25% of all ischaemic strokes), physical frailty and cognitive impairment and vascular and mixed dementia. There is no specific treatment to prevent progression of SVD. Methods: The LACunar Intervention Trial-2 is an investigator-initiated prospective randomised open-label blinded-endpoint phase II feasibility study assessing cilostazol and isosorbide mononitrate for preventing SVD progression. We aimed to recruit 400 patients with clinically evident lacunar ischaemic stroke and randomised to cilostazol, isosorbide mononitrate, both or neither, in addition to guideline secondary ischaemic stroke prevention, in a partial factorial design. The primary outcome is feasibility of recruitment and adherence to medication; key secondary outcomes include: drug tolerability; recurrent vascular events, cognition and function at 1 year after randomisation; and safety (bleeding, falls, death). Data are number (%) and median (IQR). Results: The trial commenced on 5 February 2018 and ceased recruitment on 31 May 2021 with 363 patients randomised, with the following baseline characteristics: average age 64 (56.0, 72.0) years, female 112 (30.9%), stroke onset to randomisation 79.0 (27.0, 244.0) days, hypertension 267 (73.6%), median blood pressures 143.0 (130.0, 157.0)/83.0 (75.0, 90.0) mm Hg, current smokers 67 (18.5%), educationally achieved end of school examinations (A-level) or higher 118 (32.5%), modified Rankin scale 1.0 (0.0, 1.0), National Institutes Health stroke scale 1.0 (1.4), Montreal Cognitive Assessment 26.0 (23.0, 28.0) and total SVD score on brain imaging 1.0 (0.0, 2.0). This publication summarises the baseline data and presents the statistical analysis plan. Summary: The trial is currently in follow-up which will complete on 31 May 2022 with results expected in October 2022. Trial registration number: ISRCTN14911850.

Citation

Bath, P. M., Mhlanga, I., Woodhouse, L. J., Doubal, F., Oatey, K., Montgomery, A. A., … LACI-2 Trial Investigators. (2023). Cilostazol and isosorbide mononitrate for the prevention of progression of cerebral small vessel disease: baseline data and statistical analysis plan for the Lacunar Intervention Trial-2 (LACI-2) (ISRCTN14911850). Stroke and Vascular Neurology, 8, Article e001816. https://doi.org/10.1136/svn-2022-001816

• Journal Article Type: Article
• Acceptance Date: Aug 16, 2022
• Online Publication Date: Sep 2, 2022
• Publication Date: Apr 25, 2023
• Deposit Date: Apr 26, 2023
• Publicly Available Date: Apr 26, 2023
• Journal: Stroke and Vascular Neurology
• Electronic ISSN: 2059-8696
• Publisher: BMJ Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 8
• Article Number: e001816
• DOI: https://doi.org/10.1136/svn-2022-001816
• Keywords: Cardiology and Cardiovascular Medicine; Neurology (clinical)
• Public URL: https://nottingham-repository.worktribe.com/output/10638783
• Publisher URL: https://svn.bmj.com/content/8/2/134
• Related Public URLs: https://svn.bmj.com/content/8/2/e1
• Additional Information: Authors on behalf of LACI-2 Trial Investigators.